Diabetes has a huge medical, social and economic impact. Poor compliance with parenteral insulin administration is a major problem, believed responsible for much of the end organ damage (eye, brain, and kidney) associated with the disease. Oral insulin administration would be a more convenient method and lead, therefore, to improved compliance. In addition, orally administered insulin would enter the portal blood, as does insulin from the pancreas, enabling better control of all aspects of lipid, protein and carbohydrate metabolism. Unfortunately, two major problems have prevented oral administration from becoming a viable alternative: insulin is destroyed by proteolytic enzymes; and, even in the absence of destruction, insulin is poorly absorbed form the intestinal tract. This proposal takes advantage of recent advances to deal with these problems and to enable the development of an efficient means of oral administration of insulin.